Involvement of intercellular adhesion molecule-1 in the antigen-induced infiltration of eosinophils and lymphocytes into the airways in a murine model of pulmonary inflammation.
We investigated the effects of in vivo intraperitoneal treatment with the rat monoclonal antibody (mAb), YN1.7.4 (YN1) against intercellular adhesion molecule-1 (ICAM-1) on the ovalbumin (OA)-inhalation-induced infiltration of leukocytes into the airways of OA-sensitized mice. YN1 (100 to 400 microg) given over a period of 72 h dose-dependently reduced the influx of lymphocytes and eosinophils into the bronchial lumen by > 60% and > or = 70%, respectively, when compared with saline or purified rat IgG-treated controls. Alveolar macrophages (AM) in the bronchoalveolar lavage fluid (BALF) were also decreased by > 50%. Lung tissue inflammation as determined by histopathologic examination was reduced. The number of neutrophils in the blood of OA-sensitized mice 3 days after challenge was significantly increased by treatment with YN1. However, at 24 h and 72 h after OA-challenge, the numbers of eosinophils and mononuclear cells in the bone marrow were reduced by YN1 treatment. Additionally, at 72 h after OA-challenge, the numbers of bone-marrow neutrophils were depressed. BALF levels of interleukin-5 (IL-5) and of IgA were lower for YN1-treated mice than for controls. With increasing doses of YN1, the levels of anti-ICAM-1 mAb in the plasma were proportionally increased. To correlate these results with YN1 treatment, blood and BALF T cells and BALF eosinophils were examined with flow cytometry. Blood T cells from YN1-treated mice were unable to bind phycoerythrin (PE)-labeled anti-ICAM- mAb ex vivo. These results implied that ICAM-1 on these cells was bound (occupied) by YN1 administered in vivo. Dose-related decreases were observed in the percentage and mean channel fluorescence (MCF) values of ICAM-1+ BALF T cells and eosinophils. The percentages of CD11a+ or CD49d+ eosinophils were also suppressed. Our data suggest that ICAM-1 is an important molecule involved in the recruitment of leukocytes into the airways of sensitized mice after pulmonary challenge.
Chin
J E
JE
Cell Biology and Inflammation Research, and Drug Development Toxicology, Pharmacia and Upjohn Inc., Kalamazoo, Michigan 49001, USA. jechin@am.pnu.com
Winterrowd
G E
GE
Hatfield
C A
CA
Brashler
J R
JR
Griffin
R L
RL
Vonderfecht
S L
SL
Kolbasa
K P
KP
Fidler
S F
SF
Shull
K L
KL
Krzesicki
R F
RF
Ready
K A
KA
Dunn
C J
CJ
Sly
L M
LM
Staite
N D
ND
Richards
I M
IM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism; D000941:Antigens / Q000276:immunology; D001854:Bone Marrow Cells; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology* / Q000378:metabolism; D005260:Female; D007070:Immunoglobulin A / Q000032:analysis; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D015848:Interleukin-5 / Q000032:analysis; D007962:Leukocytes / Q000276:immunology; D008168:Lung / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D011657:Pulmonary Eosinophilia / Q000276:immunology; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000941:Antigens; D007070:Immunoglobulin A; D015848:Interleukin-5; D018799:Intercellular Adhesion Molecule-1; D010047:Ovalbumin